Stem Cells In Wound Healing With Collagen Matrix as a Carrier

Wounds are a widespread problem all around the world. From a practical purpose, wounds are divided in acute and chronic. Acute wound management depends on amount and type of tissue destruction. Therefore, acute wounds could be furthermore subdivided as simple wound where only skin is missing and complex wounds when some underlying structures are involved. Complex wounds may require free flap if wound beds are poorly vascularized, devascularized or underlying tissue wouldn't accept skin graft or biologically derived extracellular matrix (BDEM). Simple wounds, on other hand, would be managed in the past by skin graft or by local flap when feasible. These management strategies commonly result in unacceptable aesthetically and/or functionally (e.g. contracture, unstable wound) outcomes and will often require secondary reconstruction.

The second class of wounds is the chronic wounds. Chronic wounds occur whenever the normally well-orchestrated reparative process does not proceed in a sequential and timely fashion from hemostasis and inflammation, through proliferation to remodeling. The process is necessarily complicated and can be delayed by many intrinsic and extrinsic factors along the way (1). Acute and chronic wounds pose a significant burden to patients, healthcare professionals, and the healthcare system, affecting more than 15.5 million patients and costing an estimated $ 500 billion annually (2-3). Based on their pathogenesis, there are four principle types of chronic wounds: venous ulcers, diabetic ulcers, arterial ischemic and pressure ulcers.

1. Venous ulcers usually occur in the legs, account for the majority of wounds, and often affecting the elderly with prior history of deep venous thrombosis (DVT). Ulcers form eventually, when cells cannot keep with rate of degradation.
2. Diabetic ulcers are seen in diabetic patients who are developing ulcers for several reasons. Neuropathy and micro-angiopathy are quite common, and these changes together with a reduced immunity set up the perfect storm for tissue breakdown in the lower extremities. Because of all these factors, exacerbated by impaired healing, even the smallest cuts or bruises can become dangerously infected.
3. PAD, is a term that covers an array of medical problems caused by obstruction of the large arteries in the arms or legs. In the advanced form of PAD, critical limb ischemia (CLI) can occur, which is a leading cause of lower limb amputations. The Angiogenesis Foundation estimates that 1.4 million people in the United States have CLI, with an estimated 350,876 new cases diagnosed each year (2).
4. Pressure ulcers comprise the fourth major type of wounds. These typically occur in people who are bedridden or whose mobility is severely limited. They are caused by a loss of blood circulation that occurs when pressure on the tissue is greater than the perfusion pressure in capillaries, thereby cutting off circulation, rendering tissue ischemic. The combination of anesthesia and paralysis is a potent inducer of tissue break down. Data from spinal cord units at Veterans Affairs Medical Centers show an alarmingly high prevalence and incidence of pressure ulcers in young soldiers paralyzed by spinal cord injuries.

Over the past decades, little improvement has been made in reducing morbidity and disability from chronic wounds (3). The best available treatment for chronic wounds achieves only a 50% healing rate that is often temporary, with an unacceptably high recurrence rate. Among the many factors contributing to "stalling" of wound healing processes, impairment in the production of cytokines by local inflammatory cells and fibroblasts and reduced angiogenesis are crucial problems (4).

The introduction of BDEMs has improved wound care significantly over the years. The most commonly used BDEM is a bovine derived collagen matrix. This bovine collagen matrix is a FDA approved wound care device comprised of a porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan and a semi-permeable polysiloxane (silicone layer). The collagen-glycosaminoglycan biodegradable matrix provides a scaffold for cellular invasion and capillary growth (5). The use of the bovine collagen matrix can improve aesthetic and functional outcomes in complex wounds with full thickness skin defects and exposure of underlying structure such as muscle, tendons, vessels or nerves. Despite its clinical benefit, a significant problem exists due to the long period required for vascularization and regeneration, which requires 3 weeks as per the manufacturer. As a result, this not only increases the cost of wound management but also decreases income potential and quality of life.